Support is requested for a series of annual Keystone Symposia meetings on the topic of Diabetes. The first meeting in the series will be held in 2015 and is entitled Diabetes and Metabolic Dysfunction, and is being organized by Jeffrey E. Pessin, Alan R. Saltiel and Deborah M. Muoio. The meeting will be held in Santa Fe, New Mexico from January 27 - February 1, 2015. The 2015 meeting will address several cutting edge aspects of molecular, cellular, tissue and integrative system metabolism that account for the metabolic defects that occur in diabetes and obesity. Several of these themes overlap with the concurrent meeting on Mitochondria, Metabolism and Heart Failure and four concurrent sessions are planned. These concurrent sessions will address distinct and novel aspects of normal and dysregulation muscle (skeletal and cardiac) intracellular signaling, mitochondria function/dynamics, aging and energy balance. The meeting organizers have selected leaders in each of these respective areas that will not only address basic and integrative mechanisms in model systems, but several will address these issues in human pathology. The diabetes-specific sessions (4) reflect several key aspects of metabolic dysregulation in which novel information is currently forthcoming causing a paradigm shift in over our previous understanding of these processes. These include new information about tissue cross-talk, the inter-relationship between the control of glucose production and fatty acid synthesis that underlies selective insulin resistance and the role of normal and dysregulated circadian rhythms on metabolic processes. These new cutting-edge advances will provide novel and exciting new findings for the basis of new future research directions.